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One of the most important features of embryonic cells is their resistence to xenobiotics, which provides a natural protection for embryos against these potentially harmful molecules. In this way, embryo cells resemble cancer cells and thus understanding the basis of this phenomenon may contribute to overcoming the multi-drug-resistance (MDR) of some tumours. Peroxisome proliferator-activated receptors (PPARs) are steroid nuclear receptors that regulate diverse biological processes such as lipid and carbohydrate metabolism, development, differentiation, apoptosis, neoplastic transformation, inflammation and regeneration of tissues. Recently it has been found that they may also regulate the expression of some MDR proteins. In this article we summarise the main known relationships between some MDR pumps and three isoforms of PPAR receptors (PPAR-alpha, PPAR-beta/delta, PPAR-gamma). We hypothesize that regulation of MDR proteins by PPAR ligands in embryos could lead to the improvement of cancer treatment.

Embryonic and tumour cells are able to protect themselves against various harmful compounds. In human pathology, this phenomenon exists in the form of multidrug resistance (MDR) that significantly deteriorates success of anticancer treatment. Cytochromes P450 (CYPs) play one of the key roles in the xenobiotic metabolism. CYP expression could contribute to resistance of cancer cells to chemotherapy. CYP epoxygenases (CYP2C and CYP2J) metabolize about 20% of clinically important drugs. Besides of drug metabolism, CYP epoxygenases and their metabolites play important role in embryos, normal body function, and tumors. They participate in angiogenesis, mitogenesis, and cell signaling. It was found that CYP epoxygenases are affected by peroxisome proliferator-activated receptorα(PPARα). Based on the results of current studies, we assume that PPARs ligands may regulate CYP2C and CYP2J and in some extent they may contribute to overcoming of MDR in patients with different types of tumours.

Three ABC transporters (MDR1, MRP1, BCRP), belonging to the family of multidrug resistance (MDR) proteins, play a crucial role in the protection mechanisms during embryogenesis and mediate drug resistance in cancer cells. The distribution of these transporters in the series of human embryonal/fetal intestine, liver and kidneys of various stages of intrauterine development (IUD) by indirect two-step immunohistochemical method was investigated. The organ- and age-specific expression patterns of these transporters were depicted and compared with the expression in adult organs. The evaluation of intestine and liver samples demonstrate differences in expression pattern of ABC transporters during IUD. On the contrary, in kidneys the age-specific localization was not observed. However, the increasing positivity from the kidney surface towards deeper, more differentiated parts was found. Hopefully, our study may contribute to elucidation of the role of multidrug resistance (MDR) pathways during IUD in man.